Format

Send to

Choose Destination
Cancer Cell. 2014 Jul 14;26(1):121-135. doi: 10.1016/j.ccr.2014.05.004. Epub 2014 Jul 4.

Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.

Author information

1
Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
2
University of Cincinnati Medical College, Cincinnati, OH 45267, USA.
3
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
4
Moores Cancer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093.
#
Contributed equally

Abstract

The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the epithelium are poorly understood. Here we show that p62 levels were reduced in the stroma of several tumors and that its loss in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism, resulting in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through the modulation of metabolism in the tumor stroma.

PMID:
25002027
PMCID:
PMC4101061
DOI:
10.1016/j.ccr.2014.05.004
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center